The metabolic response of the liver to ethanol will be studies using an approach which integrates three or four different techniques with an emphasis on functional heterogeneity and cellular diversity within the lobular unit. These techniques are: (1) Three dimensional fluorescence scanning at low temperature with high spatial resolution to determine the effect of alcohol loading on intralobular redox potential gradients; (2) Application of quantitative histochemical techniques to assess the effect of ethanol on the intralobular redox potential and phosphate potential gradients possibly present as well as the intralobular patterns of distribution of key enzymes and intermediates involved in major metabolic pathways; (3) To employ 31P NMR techniques to assess the effect of ethanol on liver phosphate metabolism in a global fashion; and (4) To apply classical morphological methods to help evaluate the results obtained by the biochemical investigations. These techniques will be applied in acute ethanol loading experiments in vitro with the isolated perfused liver or in in vivo studies and also to tissue exposed chronically to ethanol in vivo. The microchemical approach will also be used to study biopsy material. It is expected that this combined approach will provide novel information about liver metabolism in general and alcohol metabolism in particular.